Comment

Proteinuria and risk of acute kidney injury

A majority of patients developing acute kidney injury (AKI) receive medical care from their primary care physicians prior to the occurrence of conditions that predispose them to this complication.

To characterize the uNGAL concentrations in primary care patients and to assess these concentrations with regard to different reference intervals, we conducted a multicenter, cross-sectional study with random selection of general practitioners (GP) from all GP offices in seven Swiss cantons. 1000 adults (566 females; mean age 57 ± 17 years) were included.

The median absolute uNGAL was 21 ng/L. Elevated uNGAL (> 100 ng/L) together with normal kidney test results (eGFR and albuminuria) were found in 6.5% of all patients. Females had a significantly higher uNGAL than did males. Among a multitude of different clinical and laboratory variables, only age, gender, liver function parameters, WBC and CRP were significantly associated with uNGAL levels in a multivariate analysis. When examining the proposed KDIGO classification of chronic kidney disease, the uNGAL levels at the given eGFR stages changed with increasing albuminuria stages and vice versa.

Age, gender, markers of inflammation and liver function, exert influences on uNGAL concentrations. A substantial proportion of patients exhibited normal kidney testing together with elevated uNGAL, potentially identifying patients with increased renal stress and at increased risk for the development of AKI.

Protein leak in the urine is a harbinger of disruption of the glomerular filtration barrier. It also correlates with disease progression and development of ESRD. At present, therapies are aimed at decreasing proteinuria to decrease further damage to the filter and as a marker of remission. Understanding the mechanism of molecular events that lead to protein leak is vital to developing new therapeutic interventions. There has been tremendous progress over the last decade in identifying gene defects which result in hereditary proteinuric defects. This has led to identifying pathways by which these genes regulate the structure and function of the components of the filtration barrier, namely the podocytes, mesangial cells, endothelial cells, and the basement membrane. Using gene knockout mouse models, a role of tubular cells in regulating proteinuria is also emerging. In this review, we have attempted to present some of the prevailing understanding of the underlying mechanisms and physiology of proteinuria.